Our broad research objective is ultimately to understand how the skin functions so effectively as a "barrier" and how this effectiveness may be destroyed or modified by environmental influences and/or by disease. Our method of approach is a systematic study or the physical chemistry and the transport properties of human epidermis and the stratum corneum in particular. The measurement in vitro of the comparative rates of diffusion of homologous series of nonelectrolytes, ions and gases through intact and variously treated tissue is an essential part of the work. Equally important are corresponding measurements of the physical structure of the tissue; e.g., X-ray diffractions and birefringence measurements of the protein and lipid conformation; stress-strain measurements of dry, wet and solvent treated tissue and ultrastructural studies (electron microscopy and scanning e.m.). The effect of hydration or dehydration, solvent damage, solute solubility, temperature induced ultrastructural changes and the role of skin lipids on the performance of the skin as a protective "barrier" can be accurately and meaningfully studied in this way.